Tranexamic Acid for Anaemia Trial (WOMAN-3)

The Effects of Tranexamic Acid on Anaemia, Menstrual Health and the Wellbeing of Women: an International Randomised, Placebo-controlled Trial Among Menstruating Women With Anaemia

Anaemia is a common health problem in women. It is often due to iron deficiency. Anaemia is a particular problem during pregnancy and is bad for the mother and baby. It is best to treat anaemia in young women well before they get pregnant. Doctors treat anaemia with iron and vitamins. But some people get side effects when taking iron tablets and so they stop taking them. Heavy menstrual periods are a common cause of iron deficiency and even if women do take iron, because they lose so much iron in their periods, they still become iron deficient. Tranexamic acid (TXA) is a medicine used to treat heavy periods. The investigators of this study would like to find out if taking TXA with the usual iron and vitamin supplements is better at treating anaemia than taking iron and vitamin supplements alone. (Lay Summary)

Study Overview

• Status: Not yet recruiting
• Conditions: Anemia
• Intervention / Treatment: Drug: Tranexamic Acid 500 MG; Other: Matched placebo

Detailed Description

World-wide, half a billion women of reproductive age are anaemic. Anaemia has major health consequences for pregnant women and their babies. Anaemia increases the risk of ante-partum haemorrhage, prematurity, stillbirth, neonatal death, post-partum haemorrhage and maternal death. Early intervention to reduce the risk of anaemia before pregnancy offers the potential to reduce adverse maternal and birth outcomes and improve well-being across the reproductive life course.

Unfortunately, global efforts to reduce anaemia prevalence by 2025 are far off track. Anaemia worsens bleeding through multiple biological mechanisms. Anaemia increases blood flow from bleeding vessels due to reduced blood viscosity and anaemic blood clots are more susceptible to fibrinolysis. Although iron and multivitamin replacement is the mainstay of anaemia treatment, iron stores in young women depend more on menstrual iron loss than on dietary intake. Because anaemia worsens bleeding, women with anaemia have heavier menstrual periods than if they were not anaemic. For this reason, offering iron replacement without reducing menstrual iron loss may be inefficient.

The antifibrinolytic tranexamic acid (TXA) reduces menstrual bleeding by preventing blood clot breakdown. The investigators propose that giving TXA with iron and vitamin replacement will be more effective in treating anaemia than iron and vitamin replacement alone.

• Study Type: Interventional
• Enrollment (Estimated): 4000
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Dr Sima Berendes; Phone Number: +44 (0)20 7958 8161; Email: woman3@lshtm.ac.uk
• Study Contact Backup: Name: Professor Ian Roberts; Phone Number: +44 (0)20 7958 8128

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult women (aged 18 years and older)
• Having menstrual periods every 21 to 38 days that last 2 to 9 days
• Having anaemia (Hb < 120 g/L) according to point-of-care finger prick screening test
• Willing to provide informed consent and able to attend study visits during the trial period

(Individuals with known thalassaemia are eligible to participate and take the trial treatment but will not receive standard of care iron supplementation. They will continue to receive their standard care.)

Exclusion Criteria:

• Planning to get pregnant during trial period
• Already taking TXA
• Known to have contraindications to TXA treatment (including allergy to TXA or its excipients, renal impairment, active thromboembolic disease, history of venous or arterial thrombosis, history of convulsion.)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tranexamic acid (TXA); Tranexamic acid 1 gram (2x 500 mg) orally taken three times a day from the first to the last day of the menstrual period for up to 5 days, for 3 successive periods.	Drug: Tranexamic Acid 500 MG; Tablets
Placebo Comparator: Placebo; Matched placebo tablets taken three times a day from the first to the last day of the menstrual period for up to 5 days, for 3 successive periods.	Other: Matched placebo; Matched placebo tablets (inactive ingredients only, including microcrystalline cellulose, magnesium stearate BP and lactose)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anaemia	The proportion of participants with anaemia, defined as Haemoglobin (Hb) < 120 g/L (measured on venous blood)	After the 3rd and before the 4th menstrual period or by 6 months from baseline, whichever occurs first.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Haemoglobin (Hb) concentration	Hb measured on venous blood	After the 3rd and before the 4th menstrual period or by 6 months from baseline, whichever occurs first.
Severity of anaemia	Mild Anaemia (Hb=110-119 g/L); Moderate Anaemia (Hb=80-109 g/L); Severe Anaemia (Hb < 80 g/L); Hb measured on venous blood	After the 3rd and before the 4th menstrual period or by 6 months from baseline, whichever occurs first.
Ferritin	Serum ferritin (from venous blood sample) and CRP-adjusted ferritin (see below, under C-reactive protein)	After the 3rd and before the 4th menstrual period or by 6 months from baseline, whichever occurs first.
Iron deficiency	Iron deficiency defined as ferritin <15 ug/L (WHO definition) and defined as ferritin <30 ug/L, (new clinical consensus); Serum ferritin from venous blood sample; CRP-adjusted ferritin (see below, under C-reactive protein) Note: CRP-adjusted ferritin (see below)	After the 3rd and before the 4th menstrual period or by 6 months from baseline, whichever occurs first.
C-reactive protein (CRP)	The Statistical Analysis Plan (SAP) will include details on how ferritin values will be corrected by taking into account CRP levels (inflammation marker), because normal ferritin concentrations may mask an iron deficient state if inflammation is present	After the 3rd and before the 4th menstrual period or by 6 months from baseline, whichever occurs first.
Iron-deficiency anaemia	The proportion of participants with iron-deficiency anaemia, defined as presence of both anaemia (Hb<120 g/L) plus iron deficiency (ferritin <15 ug/L AND/OR <30 ug/L), measured as detailed above (using CRP-adjusted ferritin levels, as explained above)	After the 3rd and before the 4th menstrual period or by 6 months from baseline, whichever occurs first.
Menstrual blood loss	Blood loss assessed semi-quantitatively by pictorial blood assessment chart (PBAC), adapted from Higham et al (1990), DOI: 10.1111/j.1471-0528.1990.tb16249.x	During 3 menstrual periods (on average about 3 months, but no longer than 6 months from baseline)
Perceived change in menstrual blood loss	Participant's subjective assessment of change in menstrual bleeding from baseline, e.g. expressed on a Likert scale ('greatly improved' to 'much worse')	After the 3rd and before the 4th menstrual period or by 6 months from baseline, whichever occurs first.
Degree of effect of menstrual bleeding on health-related Quality of Life	SAMANTA scale (ref: Calaf, 2020, DOI: 10.1089/jwh.2018.7446 and Sinharoy 2023, DOI: 10.1016/S2214-109X(23)00416-3; Affirmative answers to two questions ('experiencing menstrual bleeding for >7 days per month' and 'being bothered by menstruation due to its Abundance') each receive 3 points, while affirmative answers to all other questions each receive 1 point ('≥3 days of heavier bleeding', 'blood spotting on clothes at night', 'worried about staining furniture', 'avoid some activities because of the need to change menstrual materials'). These values are summed, resulting in a potential range of values for the heavy menstrual bleeding score from 0 to 10.)	After the 3rd and before the 4th menstrual period or by 6 months from baseline, whichever occurs first.
Flooding	'Flooding' experienced during menstrual period (provisionally defined by Cooper 2013, DOI: 10.1111/1471-0528.17473, as "sudden overwhelming blood loss that exceeds the saturation of the menstrual products being used")	During 3 menstrual periods (on average about 3 months, but no longer than 6 months from baseline)

Collaborators and Investigators

• Sponsor: London School of Hygiene and Tropical Medicine
• Collaborators: The Jon Moulton Charity Trust
• Investigators: Study Director: Dr Sima Berendes, London School of Hygiene and Tropical Medicine (Clinical Trials Unit)

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2025
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): September 1, 2028

Study Registration Dates

• First Submitted: July 11, 2024
• First Submitted That Met QC Criteria: July 19, 2024
• First Posted (Actual): July 25, 2024

Study Record Updates

• Last Update Posted (Actual): July 25, 2024
• Last Update Submitted That Met QC Criteria: July 19, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Bleeding; Tranexamic acid; Menstruation; Anaemia; Antifibrinolytic; Menstrual health
• Additional Relevant MeSH Terms: Hematologic Diseases; Anemia; Molecular Mechanisms of Pharmacological Action; Fibrin Modulating Agents; Antifibrinolytic Agents; Hemostatics; Coagulants; Tranexamic Acid
• Other Study ID Numbers: WOMAN-3

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We are committed to sharing data for ethical research with justified scientific objectives. Until all planned analyses are completed by the LSHTM CTU Global Health Trials Group, data will be shared through a controlled access approach; thereby researchers can make formal applications for data sharing. Afterwards, we will share the anonymised dataset via the LSHTM CTU Global Health Trials Group data sharing platform at freebird.lshtm.ac.uk or a similar platform. We will make all relevant trial materials available on the trial website.
• IPD Sharing Time Frame: Once all planned analyses are completed by the LSHTM CTU Global Health Trials Group following trial completion. Data will be shared indefinitely.
• IPD Sharing Access Criteria: As described above
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No